Biochemical Aspects of Insect Venom Allergens
Insect sting allergy to bees and vespids is of common occurrence. The vespids include hornets, yellowjackets and wasps [Golden, et al., Am. Med. Assoc., 262:240 (1989)]. Susceptible people can be sensitized on exposure to minute amounts of venom proteins; as little as 2-10 .mu.g of protein is injected into the skin on a single sting by a vespid [Hoffman and Jacobson, Ann. Allergy., 52:276(1984)].
Indeed, venom allergens from insects of the Hymenoptera order have been extensively studied. These insects are bees, vespids and fire ants. The bees include honey bees (Apis melifera) and bumble bees (Bombus pennsylvanicua). The vespids include hornets (Dolichovespula spp.; Vespa crabo), yellow jackets (Vespula spp.), and paper wasps (Polistes spp.). In Table 1 are listed the venom allergens from these insects with known primary structures.
TABLE 1 ______________________________________ Cloned and/or sequenced insect venom allergens Allergen Mol. Recombinant protein.sup.3 name.sup.1 Common name Size.sup.2 unfolded folded ______________________________________ Bumble bee, Bombus pennsylvanicus Bom p 1 phospholipase A.sub.2 16 kd - - Bom p 4 protease 28 kd - - Honey bee, Apis melifera Api m 1 phospholipase A.sub.2 16 kd + + Api m 2 hyaluronidase 39 kd + + Api m 3 acid phosphatase 43 kd - - Api m 4 melittin 3 kd - - Fire ant, Solenopsis invicta Sol i 1 phospholipase A.sub.1 37 kd - - Sol i 2 30 kd - - Sol i 3 antigen 5 23 kd - + Sol i 4 20 kd - - White face hornet, Dolichovespula maculata Dol m 1 phospholipase A.sub.1 34 kd + - Dol m 2 hyaluronidase 38 kd + - Dol m 5 antigen 5 23 kd + + European hornet, Vespa crabo Vesp c 1 phospholipase A.sub.1 23 kd - - Vesp c 5 antigen 5 23 kd - - Paper wasp, Polistes annularis Pol 1 5.sup.5 antigen 5 23 kd + - Yellow jacket, Vepula vulgaris Ves v 1 phospholipase A.sub.1 34 kd + - Ves v 2 hyaluronidase 38 kd + - Ves v 5.sup.5 antigen 5 23 kd + - ______________________________________ Footnotes .sup.1 Allergen names are designated according to an accepted nomenclatur system [King et al., WHO Bulletin, 72:797 (1994)]. .sup.2 Several allergens are glycoproteins, and the molecular size given refers only to the protein portion. .sup.3 + and - signs refer to the availability of recombinant proteins. .sup.4 Sequence of antigen 5 from S. richteria is known [Smith & Hoffman, J. Allerg. Clin. Imunol., 89:293 (1992)]. .sup.5 Sequences of antigen 5s from several other vespids are known; D. arenaria [Lu et al., J. Immunol. 150:2823 (1993)], P. exclamans and P. fuscatus, and V. flavopilosa, V. germanica, V. maculifrons, V. pennsylvanica, V. spamosa and V. vidua [Hoffman et al., Int. Archs. Allergy App. Immunol., 84:24 (1987)].
There are many species of hornets (genus Dolichovespula), yellowjackets (genus Vespula) and wasp (genus Polistes) in North America [Akre, et al., "Yellowjackets of America North of Mexico," Agriculture Hand book No. 552, US Department of Agriculture (1980)]. The vespids have similar venom compositions [King, et al., Biochemistry, 17:5165 (1978); King, et al., Mol. Immunol. 20:297 (1983); King, et al., Arch. Biochem. Biophys. 230:1 (1984); King, et al., J. Allergy and Clin. Immunol., 75:621 (1985); King, J. Allergy Clin. Immunol., 79:113 (1987); Hoffman, J. Allergy and Clin. Immunol., 75:611 (1985)]. Their venom each contains three major venom allergens, phospholipase (37 kD), hyaluronidase (43 kD) and antigen 5 (23 kD) of as yet unklnown biologic function. Homologous venom allergens from hornets, yellow jackets, and paper wasps have high degrees of sequence identity ranging form about 70% for antigen 5s to about 90% for hyaluronidases [Lu et al., J. Immunol., 150:2823 (1993)].
Antigen 5 from several species each of hornets, yellowjackets and paper wasps have been cloned and/or sequenced [Fang et al., Proc. Natl. Acad. Sci., USA, 85:895-899 (1988); Lu et al., supra; Hoffman, J. Allergy Clin. Immunol., 92:707-716 (1993)]. For phospholipases and hyaluronidases only those from hornets and yellowjackets have been cloned and/or sequenced [Soladatova et al., FEBS Letters, 320:145-149 (1993); Lu et al., J. Biol. Chem., 270 :4457-4465 (1995); King et al., J. Allergy Clin. Immunol., In press (1996); Hoffman, Int. Arch. Allergy Immunol., 104:184-190 (1994)]. One common feature of these venom proteins is their varying extents of sequence homology with mammalian proteins.
White faced hornet (Dolichovespula maculata) has three forms of antigen 5. Two of these forms, Dol m 5.01 and 5.02, differ in 23% of their sequences, and they are antigenically cross reactive at both B and T cell levels [Fang et al., Proc. Natl. Acad. Sci., USA, 85:895-899 (1988); Lu et al., J. Immunol., 150:2823-2830 (1993)]. The studies described here were made with Dol m 5.02, also referred to as hornet Ag5 form 2. The amino acid sequences of Dol m 5.01 and 5.02, as well as those of the homologous antigen 5s from yellow hornet (Dolichovespula arenaria), two species of yellowjacket (Vespula maculifrons and vulgaris) and two species of papers wasps (Polistes annularis and excoamans) are given in FIG. 1.
Fire ant venom contains four allergens. They are antigen 5, phospholipase A.sub.1, and Sol i 2 and 4. Fire ant antigen 5 has about 50% sequence identity with vespid antigen 5 [Hoffman, J. Allergy Clin. Immunol., 91:71 (1995)]. Only partial sequence data is available for fire ant phospholipase, and it shows sequence identity with vespid phospholipase A.sub.1 [Hoffman, J. Allergy Clin. Immunol., 95:372 (1995)].
Bumble bee venom has two allergens of known sequences; phospholipase A.sub.2 and protease. But honey bee venom has four allergens of know sequences; acid phosphatase, phospholipase A.sub.2, hyaluronidase and a cytolytic peptide melittin. The two bee venom phospholipase A.sub.2 have extensive sequence identity and they are not-related to vespid phospholipase A.sub.1 [Hoffman, "Hymenoptia Venom Proteins" in National Toxins, R. B. Singh (ed.), Plenum Publishing 6 (1996)]. Honey bee venom hyaluronidase has about 55% sequence identity with the homologous vespid hyaluronidases.
In addition to the insect venom allergens described above, the complete amino acid sequence of several major allergens from different grass [Perez, et al., J. Biol. Chem., 265:16210 (1990); Ansari, et al., Biochemistry, 26:8665 (1989); Silvanovich, et al., J. Biol. Chem., 266:1204 (1991)], tree pollen [Breiteneder, EMBO J., 8:1935(1989); Valenta, et al., Science, 253:557 (1991)], weed pollen [Rafnar, et al., J. Biol. Chem., 266:1229 (1991); Griffith, et al., Int. Arch. Allergy Appl. Immunol., 96:296 (1991)], mites (Chua, et al., J. Exp. Med., 167:175 (1988)], cat dander [Griffith, et al., Gene., 113:263 (1992)], and mold [Aruda, et al., J. Exp. Med., 172:1529 (1990); Han, et al., J. Allergy Clin. Immunol., 87:327 (1991)] have been reported in the past few years. These major allergens are proteins of 10-40 kD and they have widely different biological functions. Nearly all allergens of known sequences have a varying extent of sequence similarity with other proteins in our environment.